Growth hormone (GH) responses to perturbation of the hypothalamic-pitu- itary-somatomedin axis have been widely used in psychiatric research as a peripheral correlate of central noradrenergic activity. Blunted GH- responses to clonidine are generally attributed to post-synaptic noradre- nergic receptor down-regulation. In addition to clonidine, the SAAD has found blunted GH responses to growth hormone-releasing factor (GRF), caffeine, and yohimbine with a trend toward blunted delayed rises in GH levels after glucose administration. The SAAD was unable to produce a paradoxical increase in GH after TRH administration, a pattern often observed in patients with major depression. These findings suggested that there might be an intrinsic abnormality in hypothalamic-GH function in panic disorder patients. To further study this possibility, the SAAD have conducted studies investigating the GH response to stimuli that mediate GH secretion via somatostatinergic or cholinergic subsystems within the hypothalamic-pituitary axis. These studies will be completed in September 1993; however, preliminary examination of data suggest that panic disorder patients have normal GH responses to stimuli that puta- tively mediate GH secretion via inhibition of somatostatin or other inhibitory neuropeptides at the level of the hypothalamus or pituitary. These observations suggest that abnormalities in GH function, when present in panic disorder patients, are probably mediated by disturbances in selective neurotransmitter or neuromodulatory systems (e.g., noradren- ergic systems) that project to the hypothalamus from other relevant brain regions. This study will be terminated in September 1993.